School of Medicine
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Assistant Professor of Pathology
Current Research and Scholarly InterestsOur lab works at the interface of immunology, cancer biology, and genomics to study cellular and molecular mechanisms of the immune response to cancer. In particular, we are leveraging high-throughput genomic technologies to understand the dynamics of the tumor-specific T cell response to cancer antigens and immunotherapies (checkpoint blockade, CAR-T cells, and others). We are also interested in understanding the impact of immuno-editing on the heterogeneity and clonal evolution of cancer.
We previously developed genome sequencing technologies that enable epigenetic studies in primary human immune cells from patients: 1) 3D enhancer-promoter interaction profiling (Nat Genet, 2017), 2) paired epigenome and T cell receptor (TCR) profiling in single cells (Nat Med, 2018), 3) paired epigenome and CRISPR profiling in single cells (Cell, 2019), and high-throughput single-cell ATAC-seq in droplets (Nature Biotech, 2019). We used these tools to study fundamental principles of the T cell response to cancer immunotherapy (PD-1 blockade) directly in cancer patient samples (Nature Biotech, 2019; Nat Med, 2019).
Clinical Assistant Professor, Pediatrics - Hematology & Oncology
BioI am currently postdoctoral research fellow pursuing immunotherapy research in the oncology department at Stanford University. My clinical training as a pediatric hematology oncology fellow at Memorial Sloan Kettering Cancer Center highlighted the desperate need for novel therapeutic options for a subtype of aggressive pediatric leukemia, Acute Myeloid Leukemia (AML). Despite our best standard of care for AML, long term survival rates range from 50-60% with an unacceptably high relapse rate of 40%. The urgent need for novel treatments inspired me to pursue a research project in adoptive immunotherapy, genetically modifying Tcells to express artificial T cell receptors, termed chimeric antigen receptors (CARs), that target AML specific antigens. In parallel to my clinical training, I constructed an AML specific CAR and demonstrated its ability to redirect T cell function mediating eradication of AML cells. As the field of CAR therapy rapidly advances, novel methods to optimize this therapeutic modality are imperative. To this end, supported by research demonstrating superior antitumor function of naïve derived effector T cells compared to central memory derived effector T cells, I am investigating whether preferential modification of naïve T cells to express CARs will generate a T cell subpopulation with increased efficacy. Consolidating my clinical and research experiences within highly academic institutes allows me to synthesize my pursuit of scientific rigor and commitment to the field of oncology, with a mission to achieve productive research and translatable results.
Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy) and of Pediatrics (Stem Cell Transplantation)
Current Research and Scholarly InterestsTransplantation of defined populations of allogeneic hematopoietic cells. Specifically, the way in which hematopoietic cell grafts alter antigen specific immune responses to allo-, auto- and viral antigens. The cellular and molecular basis of resistance to engraftment of allogeneic hematopoietic stem cells.
Melody Smith, MD, MS
Assistant Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)
BioDr. Smith is a board-certified, fellowship-trained medical oncologist and hematologist. She is an assistant professor in the Department of Medicine, Division of Blood & Marrow Transplantation and Cellular Therapy.
She is a physician-scientist who conducts extensive research. She completed a fellowship at the National Institutes of Health (NIH) in the Clinical Research Training (now, the Medical Research Scholars) Program and she was a post-doctoral researcher at Memorial Sloan Kettering Cancer Center. Her research focuses on studies evaluating strategies whereby donor T cells can be administered to improve outcomes following blood and marrow transplant. Specifically, she studies novel treatment strategies using chimeric antigen receptor (CAR) T cell therapy.
Dr. Smith has been invited to present the findings of her research at regional, national, and international conferences. At the Insights in Hematology Conference, she focused on the use of CAR T cells for blood cancers, whereas she presented her investigations on the associations between CAR T cells and the intestinal microbiome at the European Society for Blood and Marrow Transplantation. Further, at the annual meeting of the American Society of Gene & Cell Therapy, she addressed the importance of training scientists from underrepresented populations.
Dr. Smith has co-authored articles on topics within the field of cancer immunology, including cancer immunotherapy, stem cell transplantation, and CAR T cell therapy. Her work has appeared in journals, including Biology of Blood and Marrow Transplantation, Blood Advances, Leukemia, Nature, Nature Immunology, Nature Medicine, and elsewhere.
She serves a peer reviewer for publications in various journals, such as Biology of Blood and Marrow Transplantation, Haematologica, and ImmunoMedicine. She also has co-written chapters in books, including Pocket Oncology, Current Concepts and Controversies in Hematopoietic Cell Transplantation, and Advanced Concepts in Human Immunology: Prospects for Disease Control.
Dr. Smith has also earned numerous honors. The American Society of Hematology, Society for Immunotherapy of Cancer, European Society for Blood and Marrow Transplantation, and many other professional societies and organizations have recognized her achievements as a clinician, researcher, and scholar.
She is a member of the American Society of Hematology (ASH) Subcommittee on Immunotherapy and the co-chair of the Committee on Trainees and Junior Faculty for the American Society of Transplantation and Cellular Therapy (ASTCT). Other positions in service to professional organizations include co-chairing committees and task forces dedicated to promoting diversity among hematology and cell therapy specialists.
John B. Sunwoo, MD
Edward C. and Amy H. Sewall Professor in the School of Medicine and Professor, by courtesy, of Dermatology
Current Research and Scholarly InterestsMy laboratory is focused on two primary areas of research: (1) the immune response to head and neck cancer and to a tumorigenic population of cells within these malignancies called cancer stem cells; (2) the developmental programs of a special lymphocyte population involved in innate immunity called natural killer (NK) cells; and (3) intra-tumor and inter-tumor heterogeneity.